Divergent sensory pathways of sneezing and coughing

Haowu Jiang ¹⁴, Huan Cui ¹⁴, Mengyu Chen ¹, Fengxian Li ¹, Xiaolei Shen ¹, Changxiong J. Guo ¹, George E. Hoekel ¹, Yuyan Zhu ², Liang Han ², Kangyun Wu ³, Michael J. Holtzman ³, Qin Liu ¹⁵

¹Department of Anesthesiology, Washington University Pain Center, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA

²The School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA

³Pulmonary and Critical Care Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA

4These authors contributed equally

https://doi.org/10.1016/j.cell.2024.08.009

Highlights

• Sneezing and coughing are mediated by distinct sensory populations
• Nasal MrgprC11-expressing sensory neurons serve as a core “sneeze” population
• Airway SST-expressing sensory neurons mediate chemically induced cough
• Sneezing and coughing are transmitted and modulated by divergent neuropathways

Summary

Sneezing and coughing are primary symptoms of many respiratory viral infections and allergies. It is generally assumed that sneezing and coughing involve common sensory receptors and molecular neurotransmission mechanisms. Here, we show that the nasal mucosa is innervated by several discrete populations of sensory neurons, but only one population (MrgprC11⁺MrgprA3⁻) mediates sneezing responses to a multitude of nasal irritants, allergens, and viruses. Although this population also innervates the trachea, it does not mediate coughing, as revealed by our newly established cough model. Instead, a distinct sensory population (somatostatin [SST⁺]) mediates coughing but not sneezing, unraveling an unforeseen sensory difference between sneezing and coughing. At the circuit level, sneeze and cough signals are transmitted and modulated by divergent neuropathways. Together, our study reveals the difference in sensory receptors and neurotransmission/modulation mechanisms between sneezing and coughing, offering neuronal drug targets for symptom management in respiratory viral infections and allergies.